Fig. S9

The interaction of PGE2 and wnt affects regeneration in several organs (A - H) Immunohistochemical analysis of liver samples 1 day post 2/3 partial hepatectomy in C57Bl/6 and APC^Min mice. Photomicrographs were taken at 20x magnification.
(A and E) Heterozygous APC loss enhanced site-specific phosphorylation of β-catenin (S675) post liver resection.
(B and F) Heterozygous APC loss enhanced site-specific phosphorylation of phospho- GSK3β (S9). (C, D, G, H) Inhibition of prostaglandin synthesis with indomethacin (2.5 mg/kg twice daily intraperitoneal injections) resulted in undetectable levels of phospho-β-catenin (S675) and phospho-GSK3β (S9).
(I) Inhibition of PGE2 production by indomethacin diminished total β-catenin levels and site-specific phosphorylation of β-catenin (S675) and GSK3β (S9) in mice following partial hepatectomy by western blot analysis.
(J) Inhibition of PGE2 synthesis increased hepatocellular necrosis in regenerating mouse livers. Histological sections of mouse livers were examined for extensive areas of necrosis. Sections with more than 4 areas of necrosis were counted as positive. Indomethacin increased areas of necrosis in wild-type and APC^Min mice.
(K and L) Effect of PGE2 inhibition on zebrafish fin regeneration.
(K) Following amputation, the zebrafish caudal fin regenerated completely over 7 days through a wnt-mediated process of progenitor proliferation (blastema).
(L) Treatment with indomethacin (20μM) completely blocked the regenerative process compared with DMSO-treated controls (n=3/3).